Long-term Safety With Vedolizumab Intravenous (IV) in Pediatric Participants With Ulcerative Colitis (UC) or Crohn's Disease (CD)

Phase 2CompletedNCT03196427

Takeda59 enrolled

Overview

The purpose of this study is to determine the safety profile of long-term vedolizumab IV treatment in pediatric participants with UC or CD.

The drug being tested in this study is called Vedolizumab. Vedolizumab is being tested to treat pediatric participants who have moderately to severely active UC or CD. This study will look at the long-term safety profile in participants who take vedolizumab IV. Participants will continue receiving the same dose assigned from the parent study MLN0002-2003 \[NCT03138655\], which will remain blinded until week 40. The dosing regimen selected for the long-term study is intended to maintain clinical response at the lowest possible exposure. At the discretion of the investigator, participants receiving the low dose (150 or 100 milligram \[mg\]) of vedolizumab IV may be escalated to the high dose (300 or 200 mg) if the participants demonstrate disease worsening at 2 consecutive visits (scheduled or unscheduled). Participants who experience continued disease worsening during the study despite being administered vedolizumab 300 or 200 mg every 8 weeks (Q8W) will be discontinued from the study. Study duration will be until vedolizumab IV is commercially available for pediatric indication(s) in the participant's country or until other drug access programs become available (whichever comes first), the participant turns 18 years of age and can be transitioned to commercial drug, the participant withdraws from the study, or the sponsor decides to close the study (up to approximately 8 years).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Ulcerative Colitis Crohn's Disease

Interventions

VedolizumabDRUG

Vedolizumab intravenous infusion

Eligibility

Sex: ALLMin age: 2 YearsMax age: 17 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Is male or female with UC or CD and was between 2 to 17 years, inclusive, at the time of randomization for Study MLN0002-2003. (Note: A participant remains eligible to participate in this study after they reach 18 years of age if they continue to meet the inclusion criteria and do not meet any exclusion criteria.) 2. Has completed Study MLN0002-2003 and, at Week 22, achieved clinical response as defined by a reduction of partial Mayo score of \>=2 points and \>=25% from Baseline, or a reduction of the Paediatric Ulcerative Colitis Activity Index (PUCAI) of \>=20 points from baseline for participants with UC; or a reduction of the CDAI as defined by a \>=70-point decrease from Baseline or a decrease of Pediatric Crohn's Disease Activity Index (PCDAI) of \>=15 points for participants with CD. 3. May be receiving a therapeutic dose of the following drugs: * Oral 5-aminosalicylic acid (5-ASA) compounds. * Oral corticosteroid therapy (prednisone or equivalent steroid at a dose less than or equal to \[\<=\] 50 milligram per day \[mg/day\]) provided the participant was receiving this medication during prior participation in MLN0002-2003. * Topical (rectal) treatment with 5-ASA or corticosteroids. * Probiotics (example, Saccharomyces boulardii). * Antidiarrheals (example, loperamide, diphenoxylate with atropine) for control of chronic diarrhea. * Antibiotics used for the treatment of CD (i.e., ciprofloxacin, metronidazole). * Azathioprine (AZA) or 6-mercaptopurine (6-MP) or methotrexate (MTX), provided the participant was receiving this medication during prior participation in MLN0002-2003. 4. The participant's vaccinations are up to date as per inclusion criteria number 10 in MLN0002-2003. Exclusion Criteria: 1. Is female and is lactating or pregnant. 2. Has hypersensitivity or allergies to vedolizumab or any of its excipients. 3. Has withdrawn from Study MLN0002-2003. 4. Has developed any new unstable or uncontrolled cardiovascular, heart failure moderate to severe (New York Class Association III or IV), pulmonary, hepatic, renal, gastrointestinal (GI), genitourinary, hematological, coagulation, immunological, endocrine/metabolic, neurological, or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise participant safety. 5. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist prior to the administration of the first dose of study drug. 6. Currently requires major surgical intervention for UC or CD (example, bowel resection), or is anticipated to require major surgical intervention for UC or CD during the study. 7. Has other serious comorbidities that will limit his or her ability to complete the study.

Locations (23)

Cedars-Sinai Medical Center

Outcomes

Primary Outcomes

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)

AE defined as any untoward medical occurrence in clinical investigation participants administered drug; it does not necessarily have to have causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug whether or not it was considered related to the drug. TEAE was defined as an AE whose date of onset occurred on or after the first dose of study drug, or an already-present AE that worsened in intensity or frequency following the treatment start, occurring from the first dose of study drug to the day of last dose of study drug.

Time frame: From first dose of study drug up to end of follow up (up to 6.8 years)

Secondary Outcomes

Percentage of Participants With UC Who Achieved and Maintained Clinical Response Based on Complete Mayo Score

Clinical response was defined as a continued reduction in complete Mayo score of \>=3 points and \>=30 percent (%) from baseline (at initiation of MLN0002-2003) and continued decrease in rectal bleeding subscore of \>=1 point from baseline, or absolute rectal bleeding subscore of less than or equal to (\<=1) point. Mayo score was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings on endoscopy and physician rating of disease activity, each graded from 0 to 3 where 0 indicated normal and 3 indicated more severe disease. These scores were summed to give a total score range of 0 to 12; where higher scores indicated more severe disease.

Time frame: At Week 32

Percentage of Participants With CD Who Achieved and Maintained Clinical Response Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Score and Crohn's Disease Activity Index (CDAI) at Week 32

Maintenance of clinical response based on SES-CD and CDAI was defined as a 50% reduction in SES-CD score on endoscopy compared to the baseline endoscopy \[at initiation of MLN0002-2003 (NCT03138655)\]; and continued reduction in CDAI that is a \>= 70 point decrease from the baseline CDAI score at the initiation of MLN0002-2003 (NCT03138655). CDAI was a research tool used to quantify the symptoms of participants with Crohn's disease. SES-CD consisted of 3 variables: ulcer size, ulcerated and affected surfaces and presence of narrowing each graded from 0 to 3 with score of 0 means no colonic lesions or mucosal healing, and SES-CD greater than (\>) 1 indicated the presence of mucosal lesions.

Data from ClinicalTrials.gov

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Los Angeles, California, United States

Children's Hospital of Orange County

Orange, California, United States

University of California San Francisco

San Francisco, California, United States

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Nemours Childrens Specialty Care - Jacksonville

Jacksonville, Florida, United States

Children's Center for Digestive Healthcare

Atlanta, Georgia, United States

Columbia University Medical Center

New York, New York, United States

Texas Children's Hospital

Houston, Texas, United States

Seattle Children's Hospital

Seattle, Washington, United States

Hopital Necker-Enfants Malades

Paris, Île-de-France Region, France

...and 13 more locations

Time frame: At Week 32

Time to Major Inflammatory Bowel Disease (IBD) - Related Events

Time to major IBD-related events was defined as time from study treatment start to first major IBD-related hospitalization, surgery, or procedure due to UC and CD.

Time frame: Up to 6.8 years

Change From Baseline in IMPACT-III - Total Score

The IMPACT-III questionnaire was a self-reported measure with 35 closed questions encompassing 6 domains: Bowel Symptoms (7 items), Systemic Symptoms (3 items), Social Functioning (12 items), Body Image (3 items), Treatment/Interventions (3 items), and Emotional Functioning (7 items). The IMPACT-III used a 5-point Likert scale ranging from 1 to 5 for all answers. The total score was obtained by summing individual domain scores. The total score ranged from 35 to 175, with higher scores suggesting better quality of life.